Mechanisms of cytotoxic action of a series of directionally synthesized heterocyclic hydroxamic acids

   
Neganova M.E.1 , Aleksandrova Yu.R.1, Pukhov S.A.1, Klochkov S.G.1, Osipov V.N.2

1. Institute of Physiologically Active Compounds of the Russian Academy of Sciences, Chernogolovka, Russia
2. N.N. Blokhin National Medical Research Center of Oncology (N.N. Blokhin NMRC of Oncology), Moscow, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20206604332      PubMed Id: 32893823
Year: 2020  Volume: 66  Issue: 4  Pages: 332-338
Cyclic hydroxamic acids based on quinazoline-4(3H)-one and dihydroquinazoline-4(1H)-one have been synthesized. The antioxidant and iron-chelating properties of these compounds, their effect on the activity of the histone deacetylase enzyme, and their cytotoxic effect on cells of various tumor lines have been investigated. We have identified two compounds-hits, which exhibit the multipharmacological type of the antineoplastic activity. Their cytotoxic effect on cells of human lung carcinoma A549 and breast adenocarcinoma MCF-7 is obviously associated with their ability to modulate the level of reactive oxygen species and to chelate Fe(II) ions, as well as to inhibit the metalloenzymes, histone deacetylases, involved in the epigenetic regulation of tumor genesis. Thus, the synthesized hydroxamic acids may be considered as a promising basis for creating potential oncolytics.
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Keywords: hydroxamic acids, lipid peroxidation, chelation, cytotoxicity, HDAC inhibitors
Citation:

Neganova, M. E., Aleksandrova, Yu. R., Pukhov, S. A., Klochkov, S. G., Osipov, V. N. (2020). Mechanisms of cytotoxic action of a series of directionally synthesized heterocyclic hydroxamic acids. Biomeditsinskaya khimiya, 66(4), 332-338.
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